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Role of the Yersinia YopJ protein in suppressing interleukin-8 secretion by human polymorphonuclear leukocytes
Justin L Spinner1, Aaron M Hasenkrug1, Jeffrey G Shannon1
1Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 905 S. 4th St., Hamilton, Montana 59840, USA.
Abstract:
Polymorphonuclear leukocytes, in addition to their direct bactericidal activities, produce cytokines involved in the activation and regulation of the innate and adaptive immune response to infection. In this study we evaluated the cytokine response of human PMNs following incubation with the pathogenic Yersinia species. Yersinia pestis strains with the pCD1 virulence plasmid, which encodes cytotoxic Yop proteins that are translocated into host cells, stimulated little or no cytokine production compared to pCD1-negative strains. In particular, PMNs incubated with pCD1-negative Y. pestis secreted 1000-fold higher levels of interleukin-8 (IL-8 or CXCL8), a proinflammatory chemokine important for PMN recruitment and activation. Deletion of yopE, -H, -T, -M or ypkA had no effect on pCD1-dependent inhibition, whereas deletion of yopJ resulted in significantly increased IL-8 production. Like Y. pestis, the enteropathogenic Yersinia species inhibited IL-8 secretion by PMNs, and strains lacking the virulence plasmid induced high levels of IL-8. Our results show that virulence plasmid-encoded effector Yops, particularly YopJ, prevent IL-8 secretion by human PMNs. Suppression of the chemotactic IL-8 response by Y. pestis may contribute to the delayed PMN recruitment to the infected lymph node that typifies bubonic plague.
Insights
Yersinia pestis virulence factors, specifically YopJ, suppress human immune cells (PMNs) from releasing interleukin-8 (IL-8). This inhibition of IL-8 may delay immune cell recruitment during plague infections.
Area of Science:
- Immunology
- Microbiology
- Bacterial Pathogenesis
Background:
- Polymorphonuclear leukocytes (PMNs) are crucial for immune responses to infection, producing cytokines that regulate innate and adaptive immunity.
- Yersinia species are pathogenic bacteria that can cause significant infections, including plague.
- Cytokine production by PMNs plays a vital role in controlling bacterial infections.
Purpose of the Study:
- To investigate the cytokine response of human PMNs when incubated with pathogenic Yersinia species.
- To determine the role of the pCD1 virulence plasmid and its encoded Yop proteins in modulating PMN cytokine production.
- To identify specific Yop proteins involved in the suppression of interleukin-8 (IL-8) secretion.
Main Methods:
- Incubation of human PMNs with various Yersinia pestis strains, including wild-type, pCD1-negative, and strains with specific Yop gene deletions.
- Quantification of cytokine levels, particularly IL-8 (CXCL8), secreted by PMNs using established assays.
- Comparison of cytokine responses induced by Y. pestis and enteropathogenic Yersinia species.
Main Results:
- Yersinia pestis strains possessing the pCD1 virulence plasmid significantly inhibited IL-8 production by human PMNs compared to pCD1-negative strains.
- PMNs incubated with pCD1-negative Y. pestis secreted substantially higher levels of IL-8.
- Deletion of yopJ in Y. pestis strains restored significant IL-8 production, indicating YopJ's critical role in IL-8 suppression.
- Enteropathogenic Yersinia species also inhibited IL-8 secretion, with avirulent strains inducing high IL-8 levels.
Conclusions:
- Virulence plasmid-encoded Yop effectors, particularly YopJ, are responsible for suppressing IL-8 secretion from human PMNs during Yersinia infection.
- The suppression of the chemotactic IL-8 response by Y. pestis may contribute to the characteristic delayed PMN recruitment observed in bubonic plague.
- Understanding these immune evasion mechanisms is crucial for developing effective treatments against Yersinia infections.
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